Proton nuclear magnetic resonance (NMR) tomography has become an important tool in biomedical research and medical diagnosis. The image contrast mechanisms of NMR are different from X-ray imaging, and provide substantial contrast between certain soft tissues that are nearly identical using radiological techniques. Further, conventional radiological imaging techniques involve the use of high energy electromagnetic radiation associated with potential cancer induction, whereas the low energy radio waves associated with NMR poses no such risk. However, while some soft tissues provide substantial contrast using NMR techniques, others, particularly those involving the gastrointestinal tract, yield a relatively low level of contrast in proton NMR imaging. This has prompted the development of suitable NMR contrast agents. While numerous substances, such as vegetable oils and paramagnetic metal salt solutions, such as ferric chloride solutions and solutions of gadolinium oxide, have been used to visualize the lumen of the stomach and intestines in NMR tomography, none have the coating and filling characteristics which have made barium sulfate so useful in radiological applications. Moreover, many paramagnetic metal ion containing solutions e.g. those of Cu.sup.2+, Cr.sup.3+, Fe.sup.3+ and Mn.sup.2+, are generally toxic at concentrations which sufficiently shorten the spin relaxation times, T.sub.1 and T.sub.2, of the solution environment to render such solutions useful NMR contrast agents. Runge et al., Radiology, Vol. 147, pp. 789-791 (1983).
Further, since conventionally available proton NMR tomography equipment is complex in terms of operator selectable paramaters, there is a need for storage stable materials especially in the form of a collection or array, which substantially mimics the range of proton density values, spin-lattice or longitudinal relaxation (T.sub.1) values, and spin-spin or traverse relaxation (T.sub.2) values, associated with various animal tissue, for tuning such selectable parameters. Appropriate tuning of the operator selectable parameters enables the operator to optimize the desired contrast characteristics associated with NMR tomographic images, including, for example, inversion recovering images, partial saturation images, density images, spin echo images, and the like. See in general, Wehrli et al., Magnetic Resonance Imaging, Vol. 2, pp. 3-16 (1984).
It has now been surprisingly discovered that synthetic substantially non-degradable cross-linked water-swellable hydrogel materials, having in the swollen state between about 5 to about 95% water and containing functional groups which interact with water, possess nuclear magnetic resonance spin density values, and T.sub.1 and T.sub.2 values sufficiently analogous to the spectrum of values associated with mammalian tissue, such that the aqueous swollen materials are highly useful in proton NMR tomographic imaging techniques, and overcome many of the disadvantages associated with known materials and techniques.
It has been further unexpectedly discovered that those hydrogels having T.sub.1 and T.sub.2 values substantially shorter than that of gastro-intestinal viscera are highly useful as proton NMR image contrast agents.
Thus, it is an object of the instant invention to provide a method of contrasting a proton NMR tomograph of the gastro-instestinal tract, or a portion thereof, by administering to a mammal, including man, an effective image contrasting amount of a physiologically tolerable, synthetic substantially non-degradable cross-linked hydrogel having, in the aqueous swollen state, spin-lattice or spin-spin relaxation values substantially shorter than the surrounding gastro-intestinal tissue environment.
It is a further object of the instant invention to provide an aqueous coating suspension or slurry of particulate swollen synthetic substantially non-degradable cross-linked hydrogel, said hydrogel having spin-lattice or spin-spin relaxation values substantially shorter than the respective spin-lattice or spin-spin average relaxation values of gastro-intestinal viscera, for use as proton NMR contrast agents.
It is yet a further object of the instant invention to provide a collection or array of storage stable swollen cross-linked hydrogel materials possessing a range of nuclear magnetic resonance spin density values, spin-lattice relaxation values and spin-spin relaxation values, embracing at least a portion of the spectrum of such values possessed by distinct anatomic mammalian tissue, and suitable for use in NMR imaging equipment for proton NMR image contrast determinations.
These and other objects of the invention are apparent from the following disclosure.